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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.

Identifieur interne : 003311 ( Ncbi/Merge ); précédent : 003310; suivant : 003312

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.

Auteurs : Markus Hoffmann [Allemagne] ; Hannah Kleine-Weber [Allemagne] ; Simon Schroeder [Allemagne] ; Nadine Krüger [Allemagne] ; Tanja Herrler [Allemagne] ; Sandra Erichsen [Autriche] ; Tobias S. Schiergens [Allemagne] ; Georg Herrler [Allemagne] ; Nai-Huei Wu [Allemagne] ; Andreas Nitsche [Allemagne] ; Marcel A. Müller [Russie] ; Christian Drosten [Allemagne] ; Stefan Pöhlmann [Allemagne]

Source :

RBID : pubmed:32142651

Abstract

The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

DOI: 10.1016/j.cell.2020.02.052
PubMed: 32142651

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Le document en format XML

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<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
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<wicri:regionArea>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin</wicri:regionArea>
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<name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
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<div type="abstract" xml:lang="en">The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.</div>
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<Year>2020</Year>
<Month>Apr</Month>
<Day>16</Day>
</PubDate>
</JournalIssue>
<Title>Cell</Title>
<ISOAbbreviation>Cell</ISOAbbreviation>
</Journal>
<ArticleTitle>SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.</ArticleTitle>
<Pagination>
<MedlinePgn>271-280.e8</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0092-8674(20)30229-4</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.cell.2020.02.052</ELocationID>
<Abstract>
<AbstractText>The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Hoffmann</LastName>
<ForeName>Markus</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany. Electronic address: mhoffmann@dpz.eu.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kleine-Weber</LastName>
<ForeName>Hannah</ForeName>
<Initials>H</Initials>
<AffiliationInfo>
<Affiliation>Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Schroeder</LastName>
<ForeName>Simon</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Krüger</LastName>
<ForeName>Nadine</ForeName>
<Initials>N</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany; Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Herrler</LastName>
<ForeName>Tanja</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>BG Unfallklinik Murnau, Murnau, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Erichsen</LastName>
<ForeName>Sandra</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Institute for Biomechanics, BG Unfallklinik Murnau, Murnau, Germany; Institute for Biomechanics, Paracelsus Medical University Salzburg, Salzburg, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Schiergens</LastName>
<ForeName>Tobias S</ForeName>
<Initials>TS</Initials>
<AffiliationInfo>
<Affiliation>Biobank of the Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Herrler</LastName>
<ForeName>Georg</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wu</LastName>
<ForeName>Nai-Huei</ForeName>
<Initials>NH</Initials>
<AffiliationInfo>
<Affiliation>Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Nitsche</LastName>
<ForeName>Andreas</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Robert Koch Institute, ZBS 1 Highly Pathogenic Viruses, WHO Collaborating Centre for Emerging Infections and Biological Threats, Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Müller</LastName>
<ForeName>Marcel A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo>
<Affiliation>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany; Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Drosten</LastName>
<ForeName>Christian</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Virology, Berlin, Germany; German Centre for Infection Research, associated partner Charité, Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pöhlmann</LastName>
<ForeName>Stefan</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany; Faculty of Biology and Psychology, University Göttingen, Göttingen, Germany. Electronic address: spoehlmann@dpz.eu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2020</Year>
<Month>03</Month>
<Day>05</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>Cell</MedlineTA>
<NlmUniqueID>0413066</NlmUniqueID>
<ISSNLinking>0092-8674</ISSNLinking>
</MedlineJournalInfo>
<CitationSubset>IM</CitationSubset>
<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">ACE2</Keyword>
<Keyword MajorTopicYN="N">COVID-19</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="N">TMPRSS2</Keyword>
<Keyword MajorTopicYN="N">coronavirus</Keyword>
<Keyword MajorTopicYN="N">entry</Keyword>
<Keyword MajorTopicYN="N">neutralization</Keyword>
<Keyword MajorTopicYN="N">priming</Keyword>
<Keyword MajorTopicYN="N">spike</Keyword>
</KeywordList>
<CoiStatement>Declaration of Interests The authors declare no competing interests.</CoiStatement>
</MedlineCitation>
<PubmedData>
<History>
<PubMedPubDate PubStatus="received">
<Year>2020</Year>
<Month>02</Month>
<Day>06</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised">
<Year>2020</Year>
<Month>02</Month>
<Day>13</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted">
<Year>2020</Year>
<Month>02</Month>
<Day>25</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed">
<Year>2020</Year>
<Month>3</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline">
<Year>2020</Year>
<Month>3</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez">
<Year>2020</Year>
<Month>3</Month>
<Day>7</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList>
<ArticleId IdType="pubmed">32142651</ArticleId>
<ArticleId IdType="pii">S0092-8674(20)30229-4</ArticleId>
<ArticleId IdType="doi">10.1016/j.cell.2020.02.052</ArticleId>
<ArticleId IdType="pmc">PMC7102627</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Autriche</li>
<li>Russie</li>
</country>
<region>
<li>Basse-Saxe</li>
<li>Bavière</li>
<li>Berlin</li>
<li>District de Haute-Bavière</li>
<li>District fédéral central</li>
</region>
<settlement>
<li>Berlin</li>
<li>Göttingen</li>
<li>Hanovre</li>
<li>Moscou</li>
<li>Munich</li>
</settlement>
</list>
<tree>
<country name="Allemagne">
<region name="Basse-Saxe">
<name sortKey="Hoffmann, Markus" sort="Hoffmann, Markus" uniqKey="Hoffmann M" first="Markus" last="Hoffmann">Markus Hoffmann</name>
</region>
<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
<name sortKey="Herrler, Georg" sort="Herrler, Georg" uniqKey="Herrler G" first="Georg" last="Herrler">Georg Herrler</name>
<name sortKey="Herrler, Tanja" sort="Herrler, Tanja" uniqKey="Herrler T" first="Tanja" last="Herrler">Tanja Herrler</name>
<name sortKey="Kleine Weber, Hannah" sort="Kleine Weber, Hannah" uniqKey="Kleine Weber H" first="Hannah" last="Kleine-Weber">Hannah Kleine-Weber</name>
<name sortKey="Kruger, Nadine" sort="Kruger, Nadine" uniqKey="Kruger N" first="Nadine" last="Krüger">Nadine Krüger</name>
<name sortKey="Nitsche, Andreas" sort="Nitsche, Andreas" uniqKey="Nitsche A" first="Andreas" last="Nitsche">Andreas Nitsche</name>
<name sortKey="Pohlmann, Stefan" sort="Pohlmann, Stefan" uniqKey="Pohlmann S" first="Stefan" last="Pöhlmann">Stefan Pöhlmann</name>
<name sortKey="Schiergens, Tobias S" sort="Schiergens, Tobias S" uniqKey="Schiergens T" first="Tobias S" last="Schiergens">Tobias S. Schiergens</name>
<name sortKey="Schroeder, Simon" sort="Schroeder, Simon" uniqKey="Schroeder S" first="Simon" last="Schroeder">Simon Schroeder</name>
<name sortKey="Wu, Nai Huei" sort="Wu, Nai Huei" uniqKey="Wu N" first="Nai-Huei" last="Wu">Nai-Huei Wu</name>
</country>
<country name="Autriche">
<noRegion>
<name sortKey="Erichsen, Sandra" sort="Erichsen, Sandra" uniqKey="Erichsen S" first="Sandra" last="Erichsen">Sandra Erichsen</name>
</noRegion>
</country>
<country name="Russie">
<region name="District fédéral central">
<name sortKey="Muller, Marcel A" sort="Muller, Marcel A" uniqKey="Muller M" first="Marcel A" last="Müller">Marcel A. Müller</name>
</region>
</country>
</tree>
</affiliations>
</record>

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